Open-Label Dose Optimization of Methylphenidate Extended-Release Orally Disintegrating Tablet in a Laboratory Classroom Study of Children with Attention-Deficit/Hyperactivity Disorder.

To examine the efficacy, safety, and tolerability of methylphenidate extended-release orally disintegrating tablets (MPH XR-ODT) for the treatment of attention-deficit/hyperactivity disorder (ADHD) during the open-label dose-optimization/stabilization period of a phase 3 laboratory classroom study. Children (6-12 years) diagnosed with ADHD were enrolled. Treatment was initiated with MPH XR-ODT 20 mg daily. Doses were adjusted weekly by 10-20 mg during the 4-week dose-optimization period (visits 2-5) until an optimal dose was reached. The optimal dose was sustained during a 1-week stabilization period (visits 6-7). Efficacy was assessed using the ADHD Rating Scale-IV (ADHD-RS-IV) score and the Clinical Global Impression-Improvement (CGI-I) score. Adverse events (AEs) were recorded throughout the study. A secondary subgroup analysis by baseline ADHD-RS-IV score, sex, age, and weight was also performed. The mean (standard deviation [SD]) final optimized MPH XR-ODT daily dose was 41.8 (14.6) mg and ranged from 20 to 60 mg. Final optimized dose was higher for children with more severe baseline ADHD-RS-IV total scores. ADHD-RS-IV total scores decreased progressively during dose optimization, with a mean (SD) change from baseline at visit 7 of -21.4 (8.9). CGI-I scores shifted from "minimally improved" (mean [SD]: 3.1 [1.1]) at visit 3 to "much improved" (1.6 [0.6]) at visit 7. Baseline ADHD-RS-IV total score was highest for participants optimized to 40 mg (mean [standard error]: 40.0 [1.4]) and lowest for those optimized to 20 mg (34.8 [2.1]). By visit 6, mean ADHD-RS-IV score was comparable for all optimized dose groups. Common treatment-emergent AEs (≥5% of participants) included decreased appetite, upper abdominal pain, headaches, and insomnia. Dose optimization of MPH XR-ODT led to a reduction in ADHD symptoms, indicated by a decrease in ADHD-RS-IV and CGI-I scores. AEs were consistent with those of other MPH products. Clinical Trial Registry: NCT01835548 (ClinicalTrials.gov).